Evolving Radiotherapy Techniques in Paediatric Oncology

Steinmeier, Theresa; Schleithoff, Stefanie Schulze; Timmermann, Beate

doi:10.1016/j.clon.2018.12.005

Cited by 32 publications

(41 citation statements)

References 71 publications

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Section: Introductionmentioning

confidence: 99%

“…Pediatric central nervous system (CNS) malignancies are rare tumors [1] which can arise in different sites of the CNS. In recent years, patients' survival is being increased because of the advances in standard treatments [1, 2]. Radiotherapy (RT) represents a fundamental part of the recommended multimodal therapeutic approaches, even if its late toxicity is still a question of concern in this long-surviving population [3].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Proton versus Photon Radiotherapy for Pediatric Central Nervous System Malignancies: A Systematic Review and Meta-Analysis of Dosimetric Comparison Studies

Carbonara

Rito

Monti

et al. 2019

Journal of Oncology

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Background Radiotherapy (RT) plays a fundamental role in the treatment of pediatric central nervous system (CNS) malignancies, but its late sequelae are still a challenging question. Despite developments in modern high-conformal photon techniques and proton beam therapy (PBT) are improving the normal tissues dose-sparing while maintaining satisfactory target coverage, clinical advantages supporting the optimal treatment strategy have to be better evaluated in long-term clinical studies and assessed in further radiobiological analyses. Our analysis aimed to systematically review current knowledge on the dosimetric advantages of PBT in the considered setting, which should be the basis for future specific studies. Materials and Methods A PubMed and Google Scholar search was conducted in June 2019 to select dosimetric studies comparing photon versus proton RT for pediatric patients affected by CNS tumors. Then, a systematic review and meta-analysis according to the PRISMA statement was performed. Average and standard deviation values of Conformity Index, Homogeneity Index, and mean and maximum doses to intracranial and extracranial organs at risk (OARs) were specifically evaluated for secondary dosimetric comparisons. The standardized mean differences (SMDs) for target parameters and the mean differences (MDs) for OARs were summarized in forest plots (P < 0.05 was considered statistically significant). Publication bias was also assessed by the funnel plot and Egger's regression test. Results Among the 88 identified papers, a total of twelve studies were included in the meta-analysis. PBT showed dosimetric advantages in target homogeneity (significant especially in the subgroup comparing PBT and 3D conformal RT), as well as in the dose sparing of almost all analyzed OARs (significantly superior results for brainstem, normal brain, and hippocampal dose constraints and for extracranial OARs parameters, excluding the kidneys). Publication bias was observed for Conformity Index. Conclusion Our analysis supports the evidence of dosimetric advantages of PBT over photon RT, especially in the dose sparing of normal growing tissues. Confirmations from wider well-designed studies are required.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Proton versus Photon Radiotherapy for Pediatric Central Nervous System Malignancies: A Systematic Review and Meta-Analysis of Dosimetric Comparison Studies

Carbonara

Rito

Monti

et al. 2019

Journal of Oncology

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“…Technical developments have led to a transition from passive scattering proton therapy to active pencil-beam scanning (33). Scanning techniques potentially realize an even better conformal target volume coverage, and facilitate intensity-modulated proton therapy (IMPT) minimizing dose to healthy tissues (33,34). As IGRT in photon therapy, image-guided particle therapy (IGPT) is a crucial step in the treatment work ow (35).…”

Section: Studymentioning

confidence: 99%

A Baseline Survey on the Treatment Workflow and Pediatric IGRT Practice Among European Members of the Project-Based Consortium and the Pediatric Radiation Oncology Society (PROS).

Windmeijer

Bel

Jong

et al. 2020

Preprint

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Background Image-guided radiotherapy (IGRT) enables high precision tumor treatment with potential for sparing healthy tissues. The value of pediatric IGRT is widely acknowledged, but there is no consensus on ‘best practice’. We aimed to assess clinical pediatric IGRT practice among European members of the Pediatric Radiation Oncology Society (PROS) and members of our project-based consortium.Methods A survey addressing radiotherapy preparation, planning and delivery in seven treatment sites was sent to European PROS members and/or our IGRT project-based consortium (70 institutes). Responses were collected from June-September 2018.Results Of the 42 responding institutes (response rate 60%), 33 indicated to treat children. 28/33 are photon-only institutes, 3/33 are dedicated proton (‘proton-only’) institutes and 2/33 use both. Immobilization includes facial masks (in 100% of brain, craniospinal axis (CSA) and head-and-neck (H&N) treatments), and vacuum cushions (all sites, except brain and H&N). Intensity-modulated radiotherapy and volumetric-modulated arc therapy are most frequently applied ranging from 71%-81% in respectively CSA (20/28), and extremities (21/26), followed by 3D conformal radiotherapy ranging from 36%-69% in respectively H&N (10/28), and extremities (18/26). Isotropic planning target volume (PTV) margins varied widely in brain and abdomen (range, 1-10mm). The use of in-room kilovolt cone-beam computed tomography ranges from 57%-86% in respectively CSA (16/28), and thorax (24/28). Daily online imaging is used by the majority of institutes, ranging from 85%-90% in respectively extremities (22/26) and pelvis (27/30). Offline imaging protocols are used by 14%-21% in respectively H&N (4/28) and thorax (6/28).Conclusions Our survey shows comparable practice in pre-treatment imaging, planning and treatment techniques, and IGRT application among the participating European institutes. However, wide ranges in PTV margin sizes exist, supporting the need to define international ‘best practice’ guidelines for pediatric IGRT, and to aim for consensus on optimal margin definitions in view of available IGRT facilities and workflows among institutes.

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“…Herein, RT practice has largely benefited from technical improvements in treatment planning, e.g., stereotactic radiotherapy or intensity-modulated radiation therapy, that increased accuracy of dose delivery while reducing normal tissues exposure. Furthermore, therapy approaches with charged particles (mainly protons, and carbon ions) deliver only a limited amount of energy to superficial tissues while allowing the deposition of high radiation doses with high accuracy to deep-seated tumors [11,12,13]. Advances in dose delivery to improve tumor killing with minimal toxicity have also been described using ultrahigh dose-rate (FLASH) irradiation with rates above 100Gy/sec [14,15,16,17].…”

Section: Introductionmentioning

confidence: 99%

The CD73/Ado System—A New Player in RT Induced Adverse Late Effects

Leve

Wirsdörfer

Jendrossek

2019

Cancers

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Radiotherapy (RT) is a central component of standard treatment for many cancer patients. RT alone or in multimodal treatment strategies has a documented contribution to enhanced local control and overall survival of cancer patients, and cancer cure. Clinical RT aims at maximizing tumor control, while minimizing the risk for RT-induced adverse late effects. However, acute and late toxicities of IR in normal tissues are still important biological barriers to successful RT: While curative RT may not be tolerable, sub-optimal tolerable RT doses will lead to fatal outcomes by local recurrence or metastatic disease, even when accepting adverse normal tissue effects that decrease the quality of life of irradiated cancer patients. Technical improvements in treatment planning and the increasing use of particle therapy have allowed for a more accurate delivery of IR to the tumor volume and have thereby helped to improve the safety profile of RT for many solid tumors. With these technical and physical strategies reaching their natural limits, current research for improving the therapeutic gain of RT focuses on innovative biological concepts that either selectively limit the adverse effects of RT in normal tissues without protecting the tumor or specifically increase the radiosensitivity of the tumor tissue without enhancing the risk of normal tissue complications. The biology-based optimization of RT requires the identification of biological factors that are linked to differential radiosensitivity of normal or tumor tissues, and are amenable to therapeutic targeting. Extracellular adenosine is an endogenous mediator critical to the maintenance of homeostasis in various tissues. Adenosine is either released from stressed or injured cells or generated from extracellular adenine nucleotides by the concerted action of the ectoenzymes ectoapyrase (CD39) and 5′ ectonucleotidase (NT5E, CD73) that catabolize ATP to adenosine. Recent work revealed a role of the immunoregulatory CD73/adenosine system in radiation-induced fibrotic disease in normal tissues suggesting a potential use as novel therapeutic target for normal tissue protection. The present review summarizes relevant findings on the pathologic roles of CD73 and adenosine in radiation-induced fibrosis in different organs (lung, skin, gut, and kidney) that have been obtained in preclinical models and proposes a refined model of radiation-induced normal tissue toxicity including the disease-promoting effects of radiation-induced activation of CD73/adenosine signaling in the irradiated tissue environment. However, expression and activity of the CD73/adenosine system in the tumor environment has also been linked to increased tumor growth and tumor immune escape, at least in preclinical models. Therefore, we will discuss the use of pharmacologic inhibition of CD73/adenosine-signaling as a promising strategy for improving the therapeutic gain of RT by targeting both, malignant tumor growth and adverse late effects of RT with a focus on fibrotic disease. The consideration of the the...

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Evolving Radiotherapy Techniques in Paediatric Oncology

Cited by 32 publications

References 71 publications

Proton versus Photon Radiotherapy for Pediatric Central Nervous System Malignancies: A Systematic Review and Meta-Analysis of Dosimetric Comparison Studies

Proton versus Photon Radiotherapy for Pediatric Central Nervous System Malignancies: A Systematic Review and Meta-Analysis of Dosimetric Comparison Studies

A Baseline Survey on the Treatment Workflow and Pediatric IGRT Practice Among European Members of the Project-Based Consortium and the Pediatric Radiation Oncology Society (PROS).

The CD73/Ado System—A New Player in RT Induced Adverse Late Effects

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